The goals of these experiments are to isolate and characterize contact activation cofactor (CAC), and to clarify the mechanisms whereby CAC interacts with the other contact phase clotting factors--factor XI, Factor XII, and Fletcher factor--to initiate clotting in vitro. The interactions of the isolated clotting factors in the presence of different activators will be evaluated using kinetic analysis, biochemical isolation and characterization, and immunologic techniques, to attempt to identify intermediate steps leading to the formation of activated factor XI. The relationship of CAC to kininogen will also be studied.